Cysteine Article Takeaways Flashcards
Tons of toxic industrial waste products, including heavy metals are being mixed with what, being dispersed across America’s farmland.
liquid agricultural fertilizers
We are all vulnerable to what type of exposure to toxic metals?
Chronic, low level exposure
What are the heavy metals that are controversially put in fertilizers, soil, and pastures?
Aresenic, lead, cadmium, nickel, mercury, and uranium
How can acute metal toxicities be diagnosed?
Patient history and overt symptoms
Chronic, low-level exposure to heavy metals produces what type of symptoms? When do these symptoms tend to be expressed?
non-descript symptoms; overt expression of physiological aberrations are often not realized until later in life
Among the most insidious toxic metals are the sulfhydryl-reactive metals, which include which 4 metals?
- mercury (Hg)
- cadmium (Cd)
- lead (Pb)
- arsenic (As)
Which two metals are heavily deposited in the kidney?
Mercury (Hg) and Cadmium (Cd)
What is the biological half-life of cadmium (Cd) in the kidney?
On the order of decades
Which metal does not readily cross the BBB in adults, unlike mercury (Hg)?
Cadmium (Cd)
Which metal is associated more with peripheral neuropathy than with disorders of the CNS?
Cadmium (Cd)
Which metal is deposited primarily in bone?
Lead (Pb)
Which metal disrupts erythropoiesis?
Lead (Pb)
Which chronic conditions are associated with heavy metal toxicity? (list of symptoms)
fatigue, musculoskeletal pain, neurological disorders, depression, poor cognitive function, poor memory, and allergic hypersensitivity.
Which metal is the most volatile over the other sulfhydryl-reactive metals?
Mercury (Hg)
What is the primary source of chronic, low levels of Mercury (Hg) exposure?
Dental amalgams and fish
What are two ways in which mercury enters water to pollute fish?
Off-gassing from the earth’s crust and industrial pollution
How does mercury make its way up the food chain?
It is methylated by algae and bacteria in water and moves up the food chain
Which fish contain the highest concentrations of mercury?
swordfish, shark, salmon, and tuna
What are other sources of mercury (aside from off-gassing and pollution)?
combustion of fossil fuels, production of chlorine, paper and pulp, fungicides/seed preservatives, and some paints
(in some parts of the world, large amounts of Hg enter the environment as a result of careless processing of gold from ore)
What are the two major, highly absorbed subspecies of mercury?
Elemental Hg and methylmercury (MeHg)
What type and percentage of mercury is found in “silver” dental amalgams?
50% Elemental mercury
Elemental mercury is volatile and does what at room temperature?
vaporizes
Mercury is poorly absorbed if ingested, but is efficiently absorbed through which organ and means? What important barrier is crossed?
Lungs/respiration; blood brain barrier
Due to its lipophilic nature, elemental mercury has a high affinity for which membranes?
Myelin and lipid membranes
Once inside the cell, elemental mercury undergoes which reaction to become reactive Hg2+?
Elemental Hg is oxidized by catalase
MeHg, derived from fish and dimethylmercury is readily absorbed in what area?
gastrointestinal tract
MeHg can be de-methylated and oxidized into which form?
Hg2+
Once assimilated in the cell, Hg2+ and MeHg+ form covalent bonds with which two residues of proteins?
glutathione and cysteine
Once absorbed, Hg has a _____ excretion rate.
Low
A significant proportion of assimilated Hg is retained and continually accumulates in which 3 areas?
kidneys, neurological tissue, and the liver
Upon autopsy, high levels of mercury have been found in which tissues of dentists?
cardiac, thyroid, pituitary
The sulfhydryl-reactive metals have three major properties: the first is that transition metals promote what?
hydrogen peroxide and enhance the subsequent iron- and copper-induced production of lipid peroxides and the highly reactive hydroxylradical.
Which products alter membrane structure and are highly disruptive of mitochondrial function?
lipid peroxides
The pro-oxidant properties of the sulfhydryl-reactive metals is exacerbated by what effects on antioxidant processes?
inhibitory
Which two metals have a high affinity for glutathione (GSH)?
Mercury (Hg) and Cadmium (Cd)
A single atom of CD or Hg can bind to and cause irreversible excretion of what?
up to two GSH tripeptides
The metal-GSH conjugation process is desirable because of which result?
excretion of the toxic metal into the bile
The metal-GSH conjugation process is detrimental because it…
depletes the cell of GSH and thus decreases antioxidant capacity
Which two enzymes, related to GSH are inhibited by mercury?
GSH synthetase and GSH reductase
Mercury also inhibits the activities of the free radical quenching enzymes:
Catalase, superoxide dismutase, and GSH peroxidase
Inhibition of GSH peroxidase has been attributed to the formation of which complex?
mercury-selenide complex
In addition to promoting lipid peroxidation, depleting GSH and inhibiting antioxidative processes the sulfhydryl-reactive-metals disrupt the structure and function of numerous important protein through which means?
direct binding to free sulfhydryl groups.
Metal induced inhibition of Na/K/ATPase can result in what problems with astrocytes?
Swelling and destruction
What are the primary functions of astrocytes in the CNS?
homeostatic regulation of synaptic pH, Na/K and glutamate and metal sequestration
Mercury inhibits the polymerization of _________ causing the depolymerization of existing microtubules.
tubulin
Based on the study, short term and long term exposure to MeHg in drinking water resulted in a two- to three-fold up-regulation of what?
mRNA encoding for y-glutamyclcysteine synthetase (which is the rate limiting enzyme in GSH synthesis)
Which 3 metal toxicities cause fatigue?
Mercury, Lead, and Cadmium
Which metal toxicity does not cause fatigue?
Arsenic
Which metal toxicity causes depression?
Mercury
Which 2 metal toxicities lead to poor memory?
Mercury and lead
Which metal toxicity has negative effects on cognitive function?
Mercury
Which metal toxicity leads to emotional instability?
Mercury
Which metal toxicity leads to peripheral numbness or tingling?
Mercury
Which metal toxicity decreases senses of touch?
Mercury
Which metal toxicity causes hearing or vision loss?
Mercury
Which metal toxicity is responsible for hypersensitivities and allergies?
Mercury
Which heavy metal toxicity causes persistent infections, including chronic yeast overgrowth?
Mercury
Which heavy metal causes compromised immune function?
Mercury
Which metal toxicity causes cardiovascular disease?
Mercury
Which metal toxicity causes loss of apetite?
Lead
Which metal toxicity causes headaches?
Lead
Which metal toxicity leads to an inability to concentrate?
Lead
Which metal toxicity causes ADD/ADHD?
Lead
Which metal toxicity causes aberrant behavior?
Lead
Which metal toxicity causes decreased coordination?
Lead
Which metal toxicity causes irritability?
Lead
Which metal toxicity causes pain in the abdomen?
Lead
Which metal toxicity causes pain in the bones and muscles?
Lead
Which metal toxicity causes gout?
Lead
Which 2 metal toxicities causes anemia?
Lead and Cadmium
Which metal toxicity causes hypertension?
Cadmium
Which metal toxicity causes muscle and joint pain?
Cadmium
Which metal toxicity causes osteomalacia?
Cadmium
Which metal toxicity causes lumbar pain?
Cadmium
Which metal toxicity causes atherosclerosis?
Cadmium
Which metal toxicity causes kidney damage with associated urinary loss of essential minerals, amino acids, and protein?
Cadmium
Which metal toxicity causes malaise?
Arsenic
Which metal toxicity causes muscle weakness?
Arsenic
Which metal toxicity causes eczema?
Arsenic
Which metal toxicity causes dermatitis?
Arsenic
Which metal toxicity causes increased salivation and strong “garlic” breath?
Arsenic
Why is Hg relative more neurotoxic than nephrotoxic?
Activities of GSSH reductase and GSH peroxidase increase in steady state levels producing a protective and adaptive response in the renal epithelial cells, whereas neurons do not have this adaptive capacity.
Metallothioneins are a group of low molecular weight, intracellular proteins that serve as a storage depot for which 2 metals? What do they do?
Copper and zinc; “scavenge” sulfhydryl-reactive metals that enter the cell.
Metallothioneins are rich in which amino acid? (~30%) Which heavy metal do they have a higher affinity for than zinc?
Cysteine; Hg and Cd
Which amino acid inhibits transport of the MeHg-cysteine complex across the blood brain barrier?
L-Leucine
Which other amino acids (aside from leucine) compete for the L-amino acid transport system?
valine, isoleucine, phenylalanine, tyrosine, and tryptophan
Why would treatment with whey protein be helpful for heavy metal toxicity? (Whey protein contains 2.5 - 3% cysteine and 22-25% BCAAs)
Cysteine supports intracellular GSH production and metallothionein synthesis, yet provides adequate leucine to minimize the transport of metals into the CNS.
True/False: Pharmacological doses of cysteine/NAC (in the range of 1500mg/daily) can potentially exacerbate the adverse neurological effects of toxic materials.
True
Exposure to what metal directly affects uptake and release of dopamine, norepinephrine, and serotonin.
Mercury
What is the indirect effect of Hg regarding neurotransmitters?
depletion or poor assimilation of specific amino acids which are precursors of neurotransmitters.
Persistant candidiasis/dysbiosis associated with which metal burden can compromise the absorption of aromatic amino acids (phenylalanine/tyrosine/tryptophan) which are the precursors to dopamine/norepinephrine/serotonin respectively.
Mercury
Metal-induced inhibition of the 5’deiodinase enzyme is related to general peroxidative effects through the inhibition of which metal?
Mercury
HG is known to irreversibly bind to and “waste” which metal? Why does this matter?
selenium; 5’deiodinase is a selenium-dependent enzyme
Which metal may inhibit the conversion of prohormone T4 to T3 by interfering with selenium availability?
Mercury
How does mercury interfere with progesterone?
Hg binds to a free sulfhydryl group on the progesterone receptor and may thereby diminish progesterone binding and cellular response.
What are the 2 links of Hg to chronic fatigue?
- disruption in hormone metabolism (progesterone)
- binding to lipoic acid making lipoic acid unavailable for its vital role in the energy producing tricarboxylic acid
Which two metals are readily displaced from metallothionein by Hg and Cd? For what are they co-factors?
Copper and zinc; superoxide dismutase and copper is required for the synthesis of the catecholamines
Which metal is critical for wound healing, immune function, and metabolism of protein and nucleic acids?
Zinc
Ethylenediamine tetraacetic acid (EDTA) and the dithiol complexing agents have affinities for which metals?
Cu, Zn, Mn, Cr, and Mo, and can indirectly result in Mg depletion
What percentage of DMSA (a metal detoxification agent) absorbed is excreted in the urine as a cysteine-DMSA-cysteine disulfide complex?
90%; it would therefore be important to replace cysteine if using oral DMSA
